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Updated: Jan 31, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
PIK3CA Mutations and Neoadjuvant Therapy Outcome in Patients with Human Epidermal Growth Factor Receptor 2-Positive
Youjeong Seo1, Yeon Hee Park2, Jin Seok Ahn2
1Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Purpose:
PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers.
Methods:
A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients.
Results:
PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in post-NAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016).
Conclusion:
PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.
Insights
PIK3CA mutations in HER2-positive breast cancer are linked to poorer outcomes after neoadjuvant chemotherapy (NAC). These mutations predict shorter disease-free survival and lower pathologic complete response rates, especially in post-NAC specimens.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- PIK3CA mutations are implicated in resistance to neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer.
- Understanding the prognostic role of PIK3CA mutations is crucial for treatment optimization.
Purpose of the Study:
- To investigate the association between PIK3CA mutations and treatment outcomes in HER2-positive breast cancer patients receiving NAC.
- To evaluate PIK3CA mutation status in sequential specimens (pre-NAC, post-NAC, recurrent) to assess its dynamic impact.
Main Methods:
- Analysis of 100 HER2-positive breast cancer patients who underwent NAC and surgery (2004-2016).
- Sequential assessment of PIK3CA mutation status in pre-NAC, post-NAC, and recurrent tumor specimens.
- Evaluation of disease-free survival (DFS), overall survival (OS), and pathologic complete response (pCR) rates.
Main Results:
- PIK3CA mutations were detected in 17% of patients, correlating with significantly shorter DFS (58.3 vs. 119.3 months, p=0.020).
- No significant difference in pCR or OS was observed initially, but PIK3CA mutations were associated with lower pCR in post-NAC specimens (0.0% vs. 24.3%, p<0.001).
- Multivariate analysis confirmed worse DFS in the mutant PIK3CA group (HR, 3.540; p=0.050), and DFS differed significantly based on changes in mutation status over time (p=0.016).
Conclusions:
- PIK3CA mutation is a significant prognostic marker in HER2-positive breast cancer treated with NAC.
- The presence of PIK3CA mutations correlates with reduced pathologic complete response and shorter disease-free survival.
- Post-NAC PIK3CA mutation status appears particularly valuable for predicting treatment response and prognosis.
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